The topical application of cannabis-based extracts has received increased interest and attention from medical researchers in recent years, as it shows potential as a more tolerable and effective alternative to topical corticosteroids in the treatment of certain dermatoses. In parallel with the discovery of cannabinoid receptors in the skin, it has been shown that topically applied cannabis has anti-inflammatory, antipruritic, analgesic, anti-proliferative and wound-healing properties.
Cannabinoids act via the endocannabiniod system (ECS), which consists of a series of neuromodulatory lipids and receptors in the brain and central and peripheral nervous system that are activated by endogenous cannabinoids (anandamide, 2-arachidonoylglycerol) and phytocannabinoids. (Cannabinoid-1) CB 1 and (cannabinoid-2) CB 2 are the main receptors within the ECS. The two most researched phytocannabinoids are delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis, which has high levels of CBD and very low, insignificant levels of 9-THC, is also referred to as “industrial hemp” and has no psychoactive effects.
Elements of the ECS in epidermal keratinocytes, melanocytes, mast cells and in the immune regulatory system of the skin have been described in detail in the scientific literature. It has also been shown that cannabinoids suppress the proliferation and differentiation of cultured epidermal keratinocytes in vitro, alter pain perception and stimulate wound healing. They also have anti-microbial and anti-pruritic properties. Currently, more than 500 biologically active components have been discovered in plants of the Cannabis genus, of which more than 100 have been classified as phytocannabinoids (exocannabinoids).
Sebaceous gland problems; acne and rosacea
Acne is a common skin condition characterized by increased sebum production and inflammation of the sebaceous glands. Non-psychotropic phytocannabinoids have been shown to exert complex anti-acne effects by normalizing excessive sebum production, thereby reducing proliferation and alleviating inflammation in sebocytes. Due to this remarkable anti-inflammatory activity, phytocannabinoids can be used as efficient and tolerable agents for the treatment of skin inflammation.
In a single-blind split-face study, a cream containing 3% cannabis seed extract was applied twice daily to the cheeks of the study participants for 12 weeks. It was found that this treatment efficiently reduced sebum production and erythema compared to the vehicle-treated side of the face.
Wound healing properties
Considering that cannabinoid signaling regulates fibroblastic functions, proliferation and differentiation of eoidermal keratocytes as well as skin inflammation, it stands to reason that it also influences the complex process of skin wound healing. Various lines of evidence support the finding that CB 1 and in particular CB 2 can influence wound healing.
Inflammation of the skin and immune dermatitis
Studies have shown that topical application of cannabinoid receptor 1-specific agonist (CB1R) significantly accelerates the recovery of epidermal barrier function in acutely abraded skin. Anti-inflammatory activities were observed in both acute irritation and chronic irritation, which is consistent with other study results. The current evidence suggests that topical application of the CB1R agonist is an option for the treatment of acute and chronic inflammatory skin conditions, including atopic dermatitis, contact dermatitis and psoriasis.
Epidermal proliferation/psoriasis vulgaris
Cannabinoids have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 is largely expressed on leukocytes and is involved in many of the effects of cannabinoids on immune processes. Agonists have been shown to act directly on T cells, as exposure of clusters of CD3+ cells to these compounds completely inhibited their activity in a restored mixed lymphocyte response.
Since the pathogenesis of psoriasis largely involves immune properties and keratinocyte proliferation mediated by T-cell lymphocytes, cannabinoids represent an area of great scientific interest in this respect.
Topical anti-itching properties
Pruritus is an unpleasant localized or widespread itching that is a common symptom of dermatological diseases and disorders. In one study, a topical emollient containing endocannabinoids provided an average of 86% subjective relief from pruritus. In an open-label study conducted over a period of three weeks with 21 study participants suffering from uremic pruritus, a cream containing endocannabinoids was applied twice daily for three weeks. This resulted in complete elimination of pruritus in more than 38% of participants and significant relief in a further 52% of participants.
Topical applications containing endocannabinoids may be able to relieve pruritus by downregulating mast cell degranulation, inhibiting inflammatory cytokines, reducing tumor necrosis factor > (TNF->) during inflammation, or have analgesic effects of their own.
Topical analgesic properties
Studies have shown that endogenous cannabinoids (endocannabinoids) as well as synthetic cannabinoid agonists have anti-nociceptive and anti-inflammatory effects.
Skin barrier healing properties, dry skin and permeability enhancing properties
The lipids of the stratum corneum consist largely of ceramides, free fatty acids and cholesterol and are synthesized and stored in lamellar granules and extruded as precursors into the extracellular space between the stratum corneum and the stratum granolosum. A deficiency or imbalance of these lipids can lead to inadequate skin repair, skin dryness or permeability problems.
Further studies have shown that the absence of CB 1 delayed the recovery of barrier permeability, whereas it was accelerated in the absence of CB 2. Furthermore, lamellar body secretion as well as the expression of certain late differentiation marker proteins such as filaggrin, loricrin and involucrin were also found to be affected by the endocannabinoid system. This suggests that the use of cannabinoid antagonists plays a key role in the properties of skin barrier repair.
Anti-microbial properties
All five major cannabinoids (CBD, cannabichromene, cannabigerol, 9-tetrahydrocannabinol and cannbinol) also showed potent and clinically relevant effects against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains in studies.
Conclusion
After reviewing the available studies, the underlying study concludes that there is a remarkable amount of clinical evidence demonstrating the beneficial effects of topically applied cannabinoids for a variety of skin conditions.
Underlying study:
Makhakhe L.: Topical cannabidiol (CBD) in skin pathology – A comprehensive review and prospects for new therapeutic opportunities; in: S Afr Fam
Pract. 2022;64(1), a5493